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BackgroundThe COVID 19 pandemic has triggered concerns and assumptions globally about transmission of the SARS-CoV-2 virus via cash transactions.ObjectivesAssess the risk of contracting COVID-19 through exposure to SARS-CoV-2 via cash acting as a fomite in payment transactions.MethodsA quantitative microbial risk assessment was conducted for a worst-case scenario assuming an infectious person at the onset of symptoms, when virion concentrations in coughed droplets are at their highest. This person then contaminates a banknote by coughing on it and immediately hands it over to another person, who might then be infected by transferring the virions with a finger from the contaminated banknote to a facial mucous membrane. The scenario considered transfer efficiency of virions on the banknote to fingertips when droplets were still wet and after having dried up and subsequently being touched by finger printing or rubbing the object.ResultsAccounting for the likelihood of the worst-case scenario to occur by considering 1) a local prevalence of 100 COVID-19 cases/100,000 persons, 2) a maximum of about 1/5th of infected persons transmit high virus loads and 3) the numbers of cash transactions/person/day, the risk of contracting COVID-19 via person-to-person cash transactions was estimated to be much lower than once per 39,000 days (107 years) for a single person. In the general populace, there will be a maximum of 2.6 expected cases/100,000 persons/day. The risk for a cashier at an average point of sale was estimated to be much less than once per 430 working days (21 months).DiscussionThe worst-case scenario is a rare event, therefore, for a single person, the risk of contracting COVID-19 via person-to-person cash transactions is very low. At a point of sale, the risk to the cashier proportionally increases but it is still low.

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as a potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus (BCoV), as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to skin. Although we observed prolonged virus stability, our results, including a novel touch transfer method, indicate that the transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and Cmax and was slowly eliminated (mean t1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues.

The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.

A new generation of rechargeable batteries is entering the market to provide power for energy-intensive automotive, communications, utility, manual labor and manufacturing applications. These new batteries also are creating environmental and safety challenges because they are designed, used and discarded in a linear process with limited material recovery, rather than recycled in a safe closed-loop, circular manner. This stands in contrast to lead-acid batteries, which are 99 per cent recycled because the materials can be economically recycled for use in new batteries. U.S. regulations governing lead-acid batteries, however, are not applied comparably to other battery chemistries made with lithium, nickel and various rare earth, causing waste disposal issues. In addition, U.S. regulations are not reflected in other countries. This results in a “race to the bottom” in which many spent batteries (including lead-acid) are exported to poorly regulated recyclers outside the U.S. To evaluate potential closed-loop solutions to issues posed by inconsistent regulation, the current state of law governing hazardous waste disposal (including the “Universal Waste“ rule) is critically examined in this paper. An analytical tool is proposed that would enable equitable comparisons among the full range of battery chemistries (lead-acid, lithium, etc.) on a levelized basis by taking into account internal manufacture costs that are recovered in a retail battery price and external disposal costs that are not. This levelized cost model will help in the analysis of various approaches to circular materials management.

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C

Back pain is a common problem and has been shown to affect approximately 85% of the adult population at any one time. The source of this pain can be difficult to identify and the sacroiliac joint (SIJ) has been proposed as a possible pain source. Its percentage contribution to lower back pain is controversial. Clinical provocative tests for SIJ pathology have been developed but these have high intra and inter-observer variability and the significant of positive findings is unclear. This study proposes that the SIJ should not be imaged as part of a routine MRI lumbar spine series.We retrospectively reviewed the images of 353 patients who had MRI lumbar spine scans. 130 had the SIJ imaged. We recorded the clinical findings and diagnosis at referral. We reviewed the images and documented the radiological findings.SI joint pathology was most frequently identified when clinical suspected. Overall SIJ pathology found on MRI in only 0.02% of patients.We conclude that routinely imaging the SIJ in MRI lumbar spine series is not cost-effective or a useful use of resources. The SIJ should be imaged only if significant clinical findings are demonstrated.

Evanescent holes in a curved mirror will be used to provide an ultra-stable high-loss path to monitor the power in a 94 GHz transmitted beam for the Pulsed Cloud Radar on the EarthCARE satellite. Here we present details of the calculations to determine the hole size necessary and preliminary measurements on a functional model.

Objective To evaluate the effects of loteprednol etabonate (LE) 0.2% in reducing the signs and symptoms of seasonal allergic conjunctivitis. Design Randomized, double-masked, placebo-controlled, parallel group multicenter study of 6 weeks duration. Participants A total of 135 patients with signs and symptoms of seasonal allergic conjunctivitis participated. Intervention All patients received either LE 0.2% or placebo (vehicle) four times a day in both eyes for 42 days. Main outcome measures Bulbar conjunctival injection (primary sign) and itching (primary symptom) over the first 2 weeks of treatment was measured. Results A reduction in severity was seen in both LE and placebo groups for bulbar conjunctival injection (1.5 vs. 1.0 units on a 0–3 scale) and itching (3.4 vs. 3.0 units on a 0–4 scale) over the first 2 weeks. The treatment effect by these measures was −0.5 and −0.4 units in favor of LE ( P ≤ 0.008). Resolution (i.e., the proportion of patients with signs or symptoms no longer present) at day 14 strongly favored LE-treated patients (36% and 15%; 58% and 38%, for injection and itching, respectively). Both treatments were well tolerated. One patient in each treatment group (1 of 67 and 1 of 68, respectively) had an elevation of intraocular pressure of 10 mmHg or greater during the 6 weeks of treatment. Conclusions Loteprednol etabonate 0.2% was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate 0.2% had a safety profile comparable to placebo.

Whilst rules extracted from neural networks assist the explanation process, in isolation they do not illustrate the relative importance of each input parameter nor how sensitive the network's output is to these parameters. In this paper we discuss three related measures of input parameter influence which can be used to support explanation facilities for neural networks. An algorithm for generating rules from real-valued networks based on the influence measures is also presented.

Purpose: To compare the efficacy and safety of loteprednol etabonate 0.5% with those of a placebo (vehicle) in controlling anterior chamber cell and flare reaction in patients having cataract surgery with intraocular lens (IOL) implantation. Methods: This randomized, double-masked, placebo-controlled, parallel-group multicenter study comprised patients who exhibited a minimum anterior chamber inflammation (ACI) score (sum of cell and flare reaction) of 3 (0 to 9 scale) on the day after cataract removal with posterior chamber IOL implantation. All 227 patients received loteprednol etabonate 0.5% or the placebo 4 times a day in the operated eye for up to 14 days after surgery. Five patients without valid ontreatment follow-up visits were not evaluated for efficacy. Results: By the final visit, the ACI had resolved in 64% (70/109) of patients in the loteprednol etabonate group and 29% (33/113) of those in the placebo group ( P P Conclusion: Loteprednol etabonate 0.5% led to a clinically meaningful reduction in the signs and symptoms of postoperative ACI and had an acceptable safety profile when compared with a placebo.

The objective of this study was to determine the systemic exposure to loteprednol etabonate (LE) following its chronic, ocular instillation. This was a randomized, double-masked, placebo controlled, single center trial in 14 normal volunteers. Subjects were randomly assigned to receive either LE (n=10) or placebo (n=4) and instructed to instill one drop into each eye 8 times daily on Days 0 and 1 and four times daily on Days 2 through 42. Blood levels of loteprednol etabonate (LE) and its major metabolite PJ-91 (delta1 cortienic acid etabonate) in plasma, and circulating plasma cortisol levels were measured during the study. Plasma levels of LE or PJ-91 were below the level of quantitation (1 ng/mL) for all subjects in both treatment groups. Plasma cortisol levels were all within the normal range. Chronic exposure to LE at a concentration and frequency equal to or greater than the intended therapeutic dose does not result in detectable systemic levels or hypothalamic pituitary axis suppression.

Purpose To evaluate the efficacy and safety of loteprednol etabonate 0.5% as prophylactic treatment for the ocular signs and symptoms of seasonal allergic conjunctivitis. Methods In this randomized, double-masked, placebo-controlled, parallel study, 293 adults with history of seasonal allergic conjunctivitis were treated with either loteprednol etabonate or vehicle (placebo) four times daily, beginning before the onset of the allergy season and continuing for 6 weeks. The primary efficacy measure was a primary composite score (sum of itching and bulbar conjunctival injection scores). Supportive efficacy measures were the investigator global assessment and a secondary composite score (sum of tearing, erythema, chemosis, and discomfort scores), all calculated during the 21-day peak pollen season. Results The proportion of patients who never developed moderate or severe signs and symptoms of allergy during the peak pollen season in the loteprednol etabonate treatment group was greater than that in the placebo group. For the primary composite score, this efficacy criterion was reached by 94% of patients (136/145) in the loteprednol etabonate group and 78% of patients (111/143) in the placebo group ( P = .001). The magnitude of effect was similar for the investigator global assessment (86% [118/138] vs 64% [87/137]; P P = .092). None of the loteprednol etabonate-treated patients had an intraocular pressure increase of 10 mm Hg or more, whereas two placebo patients did. Conclusions Loteprednol etabonate is generally effective in prophylaxis of seasonal allergic conjunctivitis and has an acceptable safety profile.

Purpose To evaluate the safety and effectiveness of loteprednol etabonate 0.5% ophthalmic suspension in reducing the ocular signs and symptoms accompanying contact lens-associated giant papillary conjunctivitis. Methods In a randomized, double-masked, placebo-controlled, parallel-group study conducted at 14 academic or private practice clinics, 223 adults with contact lens-associated giant papillary conjunctivitis received either loteprednol or the loteprednol vehicle (placebo), one drop, four times daily for 6 weeks. Papillae, itching, contact lens intolerance, other signs and symptoms of giant papillary conjunctivitis (0-to-3 or 0-to-4 grade scales), and intraocular pressure were measured. Results The proportion of patients treated with loteprednol who at final visit demonstrated an improvement in papillae of at least one grade (78%, 85/109) was significantly greater than the proportion of those treated with placebo (51%, 56/110; P = .001). A treatment difference favoring loteprednol was seen with improvement in itching (95% vs 81%, 104/109 vs 89/110; P P = .053). Eight of 109 patients (7%, all taking loteprednol) had an intraocular pressure increase of 10 mm Hg or more on at least one visit during treatment. After discontinuation of loteprednol, intraocular pressure returned to normal levels. Both treatments were well tolerated, and no serious unexpected treatment-related medical events were reported. Conclusions The rapid therapeutic response combined with the low incidence and transient nature of any intraocular pressure increase suggests that loteprednol is an appropriate treatment for giant papillary conjunctivitis.

Primary power standards are required to provide traceability for measurements. NPL has recently built a new primary power standard for use in the 75 GHz to 110 GHz band. Compared to NPL's older standard (which has been used for several decades) the new system has a reduced thermal mass and improved thermal isolation. This gives slightly reduced overall uncertainties and an improvement in usability. Improvements in manufacturing technique offer the promise of using a similar design in the 110 GHz to 170 GHz band and work on a calorimeter for this band has begun.

A syndrome now known as Ehlers-Danlos, comprising laxity and fragility of the skin associated with hypermobility of the large joints, was published in 1892 by Tschernogobow. Ehlers-Danlos type VIIA is an extremely rare form of the syndrome. While the UK-based Ehlers-Danlos Support Group recommends that the surgical management of patients with Ehlers-Danlos VIIA should be carried out in conjunction with a plastic surgeon, there is nothing in the plastic surgery literature regarding this syndrome. The management of patients suffering from Ehlers-Danlos VIIA is highly complex, as a result of the breadth of genetic and phenotypic presentations, and resulting complications. We present a review of the literature regarding this syndrome and, in particular, the surgical problems that may be encountered. A case report outlining our experience of successfully managing this condition is also presented.

Loteprednol etabonate is a site-active corticosteroid with efficacy and safety in treating ocular inflammation at the 0.5% concentration. Evidence from dose-response studies suggested that the 0.2% concentration might be effective in treating ocular allergy.The objective of this study was to evaluate the effects of 0.2% loteprednol etabonate in reducing the signs and symptoms of seasonal allergic conjunctivitis.This was a randomized, double-masked, placebo-controlled, parallel-group multicenter study. Patients with signs and symptoms of environmental seasonal allergic conjunctivitis received either loteprednol etabonate or placebo bilaterally four times daily for 42 days.Enrolled were 133 patients (66 receiving loteprednol etahonate; 67 receiving placebo). A reduction in severity was seen in both loteprednol etabonate and placebo groups for bulbar conjunctival injection (1.3 vs 0.9 units on a 0 to 3 scale) and itching (3.5 vs 3.1 units on a 0 to 4 scale) over the first 2 weeks. The treatment effect was -0.5 and -0.6 units in favor of loteprednol etabonate (P.001). Resolution (the proportion of patients with the sign or symptom no longer present) at visit 4 (day 14) strongly favored loteprednol etabonate-treated patients over placebo-treated patients (31% and 9%, and 54% and 38%, for injection and itching, respectively). Both treatments were well tolerated. No patients in either treatment group (0 for loteprednol etabonate and 0 for vehicle) had an elevation of intraocular pressure of 10 mm Hg or greater during the 6 weeks of treatment.Loteprenol etabonate (0.2%) was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate (0.2%) had a safety profile comparable to placebo during this 6-week trial.

Appropriate for a conference relating philosophy and education, we seek ways more faithful than the truth-functional (TF) hook to understand and represent that ordinary-language conditional which we use in, e.g., modus ponens, and that conditional’s remote and counterfactual counterparts, and also the proper negations of all three. Such a logic might obviate the paradoxes caused by T-F representation, and be educationally fruitful. William and Martha Kneale and Gilbert Ryle assist us: "In the hypothetical case in which p, it is inferable, on the basis that p and at least in the given context, that q." "Inferable" is explained. This paraphrase is the foundation of the logic of hypothetical inferability ("HI logic"). It generates the negative but non-TF device "hib" (= "there is a hypothetical-inferability bar against the conjoint proposition that"), followed by a bracketed conjunction. This is an enriched negative: "hib (p . -q)" is stronger than "-(p . -q)," and "-hib" ("dash hib" = "there is no h-i bar...") offers us "-hib (p . -q)," weaker than "p . -q." Thus equipped, we can test deductive arguments by the CI ("Compatible-orincompatible?") method explained, and explode paradoxes. The paraphrase, "hib," and the CI method are fruitful in training students to understand this conditional, and to demonstrate genuine validity or invalidity.

The results of the study by Flinn et al 1 reemphasize that the primary and secondary prevention of pulmonary embolism in a high-risk population may reduce adverse outcomes. We were impressed by the authors' 94% accuracy rate for venous duplex ultrasound scanning. This is not a common experience in the asymptomatic deep vein thrombosis (DVT) population. Pooled data from studies using venography (the "gold standard") systematically show a 79% sensitivity using venous duplex ultrasound scanning for proximal DVT and a positive predictive value of 69%, 2 values that drop in patients with craniotomy to 38% and 56%, respectively. 3 The authors' accuracy rate was derived from "an extended period of experience," 4 with no mention of the number of patients or the method of evaluation used, which leaves the readers to surmise its validity. When the authors quote "accuracy" rate, are they referring to the positive predictive value? In the

Two chemical derivatives of delta-1-tetrahydrocannabinol were evaluated in a randomized, double-masked study, administered as a single oral dose to a group of ocular hypertensive patients. One of the compounds (BW146Y) was found to have a significant intraocular pressure lowering effect that was independent of orthostatic blood pressure changes, although such changes did occur in some patients. The other compound (BW29Y) was ineffective in lowering intraocular pressure at the doses tested. Psychological and performance parameters were measured, and except for a time production test among the BW29Y group, these parameters were not significantly affected by the test drugs. Patients receiving both drugs experienced mild subjective side effects.

In a placebo-controlled, double-blind study we evaluated the safety and kinetics of a new narcotic antagonist, nalmefene, after 2, 6, 12, and 24 mg intravenous doses to healthy men. At each dose level four subjects received active drug and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness. The plasma concentration-time data were best fit with a triexponential equation, and the terminal elimination phase had a harmonic mean t1/2 of 8 to 9 hours. Only about 5% of the dose was excreted in the urine as intact nalmefene, with up to 60% excreted as nalmefene glucuronide. Although intersubject differences were noted, mean or dose-normalized mean kinetic parameters such as clearance, steady-state volume of distribution, terminal t1/2, and AUC showed no consistent trends related to increasing doses, indicating that nalmefene has linear pharmacokinetics.

The aim of these two studies was to evaluate the safety and pharmacokinetics of oral nalmefene, a new orally effective opioid antagonist. In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. Model-independent pharmacokinetic analysis of the plasma concentration-time data showed that nalmefene was rapidly absorbed and had an elimination half-life that ranged from seven to 15 hours (mean, 10.7 hr). There was a good linear relationship (r = .97) between administered dose and total area under the curve at each dose level. Only about 4% of the dose was excreted in the urine as unchanged nalmefene, whereas up to 60% was excreted as a beta-glucuronidase/sulfatase hydrolysable conjugate(s) of nalmefene. In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.(ABSTRACT TRUNCATED AT 250 WORDS)